Evidence map›Paper›PMID 23463102›Full record

ArticleThe EMBO journal2013

PDK1 regulates VDJ recombination, cell-cycle exit and survival during B-cell development.

Ram K C Venigalla, Victoria A McGuire, Rosemary Clarke, Janet C Patterson-Kane, Ayaz Najafov, Rachel Toth, Pierre C McCarthy, Frederick Simeons, Laste Stojanovski, J Simon C Arthur

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.5field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. A Microbiota- and IL-15-Dependent Innate-Like B Cell Progenitor Expressing E4BP4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. PDK1 Is Required for Maintenance of CD4Journal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  7. Article
  8. Article
  9. [The role of PDK1 in the transition of endothelial to hematopoietic cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018
    Article
  10. Article
  11. The Journal of biological chemistry · 2017
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. The PI3K pathway in B cell metabolism.Critical reviews in biochemistry and molecular biology · 2016
    Review
  17. Article
  18. Article
  19. Article
  20. PDK1 regulates B cell differentiation and homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Ram K C VenigallaMRC Protein Phosphorylation Unit, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, UK. ramkumar.venigalla@babraham.ac.uk
Victoria A McGuire
Rosemary Clarke
Janet C Patterson-Kane
Ayaz Najafov
Rachel Toth
Pierre C McCarthy
Frederick Simeons
Laste Stojanovski
J Simon C Arthur
University of Dundee · GBMRC Protein Phosphorylation and Ubiquitylation Unit · GBUniversity of Glasgow · GB

Funding

Arthritis Research UKMedical Research Council MC_U127081014Medical Research Council MC_UU_12016/10Wellcome TrustWellcome Trust 0181867/Z/06/Z
6 · The paper itself

Abstract

Phosphoinositide-dependent kinase-1 (PDK1) controls the activation of a subset of AGC kinases. Using a conditional knockout of PDK1 in haematopoietic cells, we demonstrate that PDK1 is essential for B cell development. B-cell progenitors lacking PDK1 arrested at the transition of pro-B to pre-B cells, due to a cell autonomous defect. Loss of PDK1 decreased the expression of the IgH chain in pro-B cells due to impaired recombination of the IgH distal variable segments, a process coordinated by the transcription factor Pax5. The expression of Pax5 in pre-B cells was decreased in PDK1 knockouts, which correlated with reduced expression of the Pax5 target genes IRF4, IRF8 and Aiolos. As a result, Ccnd3 is upregulated in PDK1 knockout pre-B cells and they have an impaired ability to undergo cell-cycle arrest, a necessary event for Ig light chain rearrangement. Instead, these cells underwent apoptosis that correlated with diminished expression of the pro-survival gene Bcl2A1. Reintroduction of both Pax5 and Bcl2A1 together into PDK1 knockout pro-B cells restored their ability to differentiate in vitro into mature B cells.

Indexed as

3-Phosphoinositide-Dependent Protein KinasesAnimalsB-LymphocytesCell Cycle CheckpointsCyclin D3Gene Knockdown TechniquesIkaros Transcription FactorImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsInterferon Regulatory Factor-4Interferon Regulatory Factor-8Interferon Regulatory FactorsMiceMice, TransgenicMinor Histocompatibility AntigensPAX5 Transcription Factor3-Phosphoinositide-Dependent Protein KinasesBCL2-related protein A1Ccnd3 protein, mouseCyclin D3Ikaros Transcription FactorIkzf3 protein, mouseImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsInterferon Regulatory Factor-4Interferon Regulatory Factor-8Interferon Regulatory FactorsMinor Histocompatibility AntigensPax5 protein, mousePAX5 Transcription FactorPdpk1 protein, mouseProtein Serine-Threonine KinasesProto-Oncogene Proteins c-bcl-2Trans-Activators

Identifiers

PMID23463102
PMCPMC3616287
OpenAlexW1977064462

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.